Inotuzumab ozogamicin combined with chemotherapy in pediatric B-cell precursor CD22 acute lymphoblastic leukemia: results of the phase IB ITCC-059 trial.

Inotuzumab ozogamicin (InO) is a CD22-directed antibody conjugated with calicheamicin. The phase IB of the ITCC-059 trial tested InO combined with chemotherapy in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Relapsed /refractory CD22+ BCP-ALL pediatric patients were enrolled.

Cerebral Spinal Fluid Parameters Following CD19-Targeted Therapies in Children and Young Adults.

The presence of leukocytes in the cerebral spinal fluid (CSF) of patients with acute lymphoblastic leukemia may indicate a relapse in the central nervous system. CD19-directed immunotherapy may increase the blood-brain barrier permeability, leading to neurologic toxicity and infiltrate the CNS. We studied the CSF cell and protein content in 71 consecutive patients who received either CD19 chimeric antigen receptor T cells or blinatumomab.

Improved Outcome Following Busulfan-Based Conditioning in Children with Functional Neutrophil Disorders Undergoing Hematopoietic Stem Cell Transplant from HLA-Matched Donors.

Hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for chronic granulomatous disease (CGD) and leukocyte-adhesion deficiency (LAD), but both diseases have high rates of graft failure in transplant and patients with these diseases are often referred to HSCT with significant comorbidity. The intensity of the conditioning regimen should be balanced between the need to ensure durable engraftment and to minimize toxicity when transplanting young children with infections and organ damage. We report on 26 children transplanted at our institution with CGD and LAD over 24 years.

αβ /CD19 -depleted haploidentical stem cell transplantation for children with acute leukemia: Is there a protective effect of increased γδ T-cell content in the graft?

Background: Haploidentical hematopoietic stem cell transplantation (HSCT) with depletion of αβ T cells and CD19 B cells has emerged as a viable alternative to traditional donors for treating acute leukemia in children. As the use of this innovative approach continues to grow and more experience is gained, it is essential to identify and comprehend the key factors that contribute to successful transplantation and improved outcomes.

Methods: We conducted a retrospective analysis of single-center data from 27 children with acute lymphoblastic leukemia and 11 children with acute myeloid leukemia who underwent haploidentical HSCT with depletion of αβ T cells and CD19 B cells between the years 2013 and 2020.

CD19 CAR T-cells for pediatric relapsed acute lymphoblastic leukemia with active CNS involvement: a retrospective international study.

Relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) may occur in the central nervous system (CNS). Most clinical trials of CAR T-cell therapy excluded patients with active CNS leukemia, partially for concerns of neurotoxicity. Here, we report an international study of fifty-five children and adolescents who received CAR T-cell therapy for relapsed BCP-ALL with CNS involvement at the time of referral.

Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase II trial.

Inotuzumab Ozogamicin is a CD22-directed antibody conjugated to calicheamicin, approved in adults with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (BCP-ALL). Patients aged 1-18 years, with R/R CD22 + BCP-ALL were treated at the RP2D of 1.8 mg/m.

Invasive Fusariosis in Pediatric Hematology/Oncology and Stem Cell Transplant Patients: A Report from the Israeli Society of Pediatric Hematology-Oncology.

Invasive Fusarium species infections in immunocompromised patients occur predominantly in those with hematological malignancies. Survival rates of 20−40% were reported in adults, but data in children are limited. Our retrospective, nationwide multicenter study of invasive fusariosis in pediatric hematology/oncology and stem cell transplant (SCT) patients identified twenty-two cases.

Parameters of long-term response with CD28-based CD19 chimaeric antigen receptor-modified T cells in children and young adults with B-acute lymphoblastic leukaemia.

CD28-based CD19 chimaeric antigen receptor-modified (CAR-)Tcells were recently FDA-approved for adult acute lymphoblastic leukaemia (ALL). We report long-term outcome of 37 children and young adults treated with autologous CD19 CAR-T cells. The complete remission rate was 86%, of which 71% were polymerase chain reaction (PCR) minimal residual disease (MRD)-negative, 14% were MRD-negative by flow cytometry, and 14% were PCR MRD-positive.

Bortezomib-based Anthracycline-free Induction for Pediatric Relapsed ALL as a Bridge to Immunotherapy.

Background: Immunotherapy may lead to durable remissions in patients with relapsed and refractory acute lymphoblastic leukemia (R/R ALL). Patients receiving immunotherapy with a lower disease burden tend to have improved long-term outcomes and less toxicity. Thus, an induction protocol to achieve lower disease burden is required.

Improved transplant outcomes with myeloablative conditioning for hemophagocytic lymphohistiocytosis in HLA-matched and mismatched donors: a national multicenter retrospective study.

We report the results of national retrospective study of 45 children with hemophagocytic lymphohistiocytosis (HLH) who underwent allogeneic hematopoietic stem-cell transplantation (HSCT) in Israel between the years 2000-2018. Donors were either HLA-matched (n = 26), partially mismatched (n = 7), haploidentical (n = 8), or cord-blood (n = 4). Myeloablative conditioning (MAC) was used in 20 procedures, and reduced-intensity conditioning (RIC) in 25.

Characteristics and risk factors of infections following CD28-based CD19 CAR-T cells.

CAR T-cells are approved for the treatment of relapsed and refractory leukemia and lymphoma. Here, we studied the infectious complications in 88 patients treated with CD28-based CD19 CAR T-cells. Overall, 36 infections were documented in 24 patients within the first month after CAR T-cell infusion: Six events of bacteremia, sixteen focal bacterial infections, and fourteen systemic or localized viral infections.

A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study).

This phase 1 study investigated the recommended phase 2 dose (RP2D) of inotuzumab ozogamicin (InO), a CD22-directed antibody-drug conjugate, in pediatric patients with multiple relapsed/refractory (R/R) CD22+ acute lymphoblastic leukemia (ALL). Patients (age ≥1 year or <18 years) received 3 doses of InO (days 1, 8, and 15) per course. Dose escalation was based on dose-limiting toxicities (DLTs) during course 1.

Venous Thromboembolism and Its Risk Factors in Children with Acute Lymphoblastic Leukemia in Israel: A Population-Based Study.

Venous thromboembolism (VTE) is a serious complication of acute lymphoblastic leukemia (ALL) therapy. The aim of this population-based study was to evaluate the rate, risk factors, and long-term sequelae of VTE in children treated for ALL. The cohort included 1191 children aged 1-19 years diagnosed with ALL between 2003-2018, prospectively enrolled in two consecutive protocols: ALL-IC BFM 2002 and AIEOP-BFM ALL 2009.

Feasibility of leukapheresis for CAR T-cell production in heavily pre-treated pediatric patients.

Background: Autologous CD19 chimeric-antigen receptor (CAR) T-cells are an effective salvage therapy for patients with relapsed or refractory B cell malignancies. The essential first step in the production is the collection of mature lymphocytes through leukapheresis. It is a challenging procedure given the fact patients are heavily pretreated and the special considerations of pediatric apheresis.

Mucormycosis in children with haematological malignancies is a salvageable disease: a report from the Israeli Study Group of Childhood Leukemia.

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004-2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres.

Poorer outcome of childhood acute lymphoblastic leukemia in the Bedouin population: A report from the Berlin-Frankfurt-Muenster-based Israeli national protocols.

Background: Therapy outcomes for childhood acute lymphoblastic leukemia (ALL) had substantially improved in the last decades, but variability across racial and ethnic groups was identified in some clinical studies. In this study, we aimed to investigate whether such a difference in outcome is found in the diverse ethnicities in Israel as well.

Methods: A retrospective study was conducted among 1154 patients (855 Jews, 195 Muslims, 52 Bedouins, 26 Druze, and 26 others) aged 1 to 21 years, who were diagnosed with ALL between 1989 and 2011 and were treated according to the same Berlin-Frankfurt-Muenster-based Israel National Study protocols.

Haploidentical hematopoietic stem cell transplantation with αβTCR+/CD19+ depletion in pediatric patients with malignant and non-malignant disorders.

Haploidntical hematopoietic stem cell transplantation has been increasingly used in recent years for patients without a matched donor. The αβTCR+/CD19+ depletion technique provide a graft that is enriched with CD34 cells, γδ-T-cells and natural killer. The current experience with αβTCR+/CD19+ depleted grafts in pediatric patients with malignant and non-malignant disorders, demonstrated rapid engraftment, improved immune reconstitution and low risk of GVHD.

Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: Report from the Israeli Study Group of Childhood Leukemia.

Tremendous progress in the therapy of pediatric acute lymphoblastic leukemia (ALL) has been achieved through combination cytotoxic chemotherapy, leading to high cure rates, at the cost of significant life-threatening toxicity. The bispecific T-cell engager blinatumomab, recently approved for relapsed/refractory ALL, has a unique nonmyelotoxic toxicity profile. As blinatumomab causes B-cell depletion, the safety of its use during severe chemotherapy-induced toxicity is unclear.

Immune reconstitution after HSCT in SCID-a cohort of conditioned and unconditioned patients.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the effective mean of immune restoration in severe combined immunodefiency (SCID). Usually, HSCT without cytoreductive conditioning is attempted. Nevertheless, conditioning procedures are still preferred in a subset of patients.

Early and late hematologic toxicity following CD19 CAR-T cells.

Autologous T cells transduced with CD19-directed chimeric antigen receptors have recently been approved by several regulatory agencies for the treatment of relapsed and refractory leukemia and lymphoma, after demonstrating remarkable remission rate in advanced patients. The most common adverse events reported are cytokine-release syndrome (CRS), neurotoxicity, and hematologic toxicity. Here, we focus on early and late cytopenia occurring after CD19 CAR-T cells in 38 patients treated with CD19 CAR-T cells.

Sustained Response to Imatinib in a Pediatric Patient with Concurrent Myeloproliferative Disease and Lymphoblastic Lymphoma Associated with a CCDC88C-PDGFRB Fusion Gene.

Background: The WHO defined myeloid and lymphoid neoplasms (MLN) with eosinophilia associated with PDGFRB, PDGFRA, FGFR1 rearrangements as a new entity in 2016. PDGFRB-rearranged MLN sensitive to imatinib were described in adult patients. We report the first pediatric patient with PDGFRB-rearranged myeloproliferative disorder associated with T-lymphoblastic lymphoma bearing the t(5; 14)(q33;q32) translocation who was successfully treated with imatinib only.